Enhanced induction of LPS-induced fibroblast MCP-1 by interferon-gamma: involvement of JNK and MAPK phosphatase-1.
IFN-gamma has significant immunoregulatory activity and plays an important role in both innate and adaptive immunity. Additive effects of IFN-gamma and the Toll-like receptor ligand LPS has been investigated in macrophages, but in fibroblasts is incompletely understood. IFN-gamma and LPS synergistically induced MCP-1 and NO release in primary murine dermal fibroblasts. IFN-gamma enhanced LPS-induced JNK and p38 MAPK phosphorylation but had no effect on NF-kappaB activity. The induction of both MCP-1 and NO was attenuated by inhibition of JNK but not p38 MAPK. Serine 727 STAT1 phosphorylation by IFN-gamma was increased by LPS, and this was also attenuated by inhibition of JNK but not p38 MAPK. IFN-gamma inhibited the basal expression of MAPK phosphatase-1, a negative regulator of MAPK signaling pathway. These results suggest that enhancement of LPS-induced JNK activation by IFN-gamma associated with inhibition of MAPK phosphatase-1 may be one of the mechanisms of additive effects between IFN-gamma and LPS in fibroblasts.
Yamana
Jiro
J
The Centre for Inflammatory Diseases, Monash Medical Centre Clayton, Monash Institute of Medical Research, Department of Medicine, Monash University, Locked Bag No. 29, Clayton, Melbourne 3168, Australia. jyamanajyamana@yahoo.co.jp
Santos
Lanie
L
Morand
Eric
E
D000818:Animals; D000873:Anthracenes / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology*; D054638:Dual Specificity Phosphatase 1 / Q000276:immunology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism
D000873:Anthracenes; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D007093:Imidazoles; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011725:Pyridines; D050794:STAT1 Transcription Factor; C432165:pyrazolanthrone; D009569:Nitric Oxide; D007371:Interferon-gamma; D048031:JNK Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1; C093642:SB 203580